Diabetes has reached epidemic proportions in both developed and developing countries, and the cost of treating individuals with complications resulting from uncontrolled hyperglycemia is a major economic burden in the world. A promising but still unrealized goal of efforts to improve diabetes therapy is the identification of novel factors that promote pancreatic β cell (β cell) regeneration, with the long-term goal of increasing functional β cell mass in patients with either type 1 or type 2 diabetes. Reduced functional β cell mass is a central feature in both forms of the disease and in diabetes associated with obesity (Muoio, D. M., and Newgard, C. B. (2008). Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat. Rev. Mol. Cell Biol. 9, 193-205). While autoimmune destruction of β cells is the major cause of β cell loss in type 1 diabetes, a failure of β cells to compensate for ambient insulin resistance leads to uncontrolled hyperglycemia in type 2 diabetes.
Thus, what is needed are compositions and methods effective in promoting β cell proliferation, especially in subjects that are in need of improved β cell function.